Tacrolimus Treatment for Refractory Autoimmune Cytopenia

Autoimmune cytopenia, including autoimmune hemolytic anemia (AIHA), pure red cell aplasia (PRCA), Evans syndrome (ES), usually has good responses to steroids therapies as first line, but there is a considerable percentage of patients who relapse, become refractory or dependent on steroids to maintain an acceptable level of hemoglobin or platelets. The effects of the second line therapy are also not satisfactory and sometimes not available. The investigators aim to explore the efficacy and side-effect of tacrolimus for refractory autoimmune cytopenia.

Study Overview

• Status: Unknown
• Conditions: Pure Red Cell Aplasia; Autoimmune Hemolytic Anemia; Evans Syndrome
• Intervention / Treatment: Drug: Tacrolimus

Detailed Description

Tacrolimus binds FKBP12 with high affinity after entry into cytoplasm, suppresses calcineurin activity and prevents nuclear translocation of transcription factors such as NF-AT that are involved in IL-2 gene transcription. As a result, T-cell activation is inhibited with a subsequent reduction in the production of cytokines that include IL-2, TNF-α, IL-3, IL-4, IFN-γ, IL-6 and IL-10; B-cell activation, class-switching and immunoglobulin production are also attenuated. Reports on the use of tarcrolimus in the treatment of autoimmune cytopenia are anecdotal and describe therapy with a variety of drug dosages.

The purpose of this study is to evaluate the effect of tacrolimus on patients with refractory autoimmune cytopenia, the side-effects will be documented and plasma concentration of tacrolimus will be monitor.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ruoxi Zhang, M.D.; Phone Number: +86 18510064839; Email: rx_zh15@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Ruoxi Zhang, MD; Phone Number: +86 18510064839; Email: rx_zh15@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Refractory autoimmune cytopenia, including autoimmune hemolytic anemia, pure red cell aplasia, Evans syndrome.
• 18-80 years old.
• No response or intolerant to first and second line therapies.
• ECOG Performance Status of 0-2
• Written informed consent.

Exclusion Criteria:

• Other diseases which might cause hematological abnormalities.
• Response and well tolerate to first or second line therapy.
• Patients who are under 18-year-old or over 80-year-old.
• Pregnant or lactating.
• Patients unwilling to or unable to comply with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efficiency of tacrolimus on autoimmune cytopenia; A prospective research of the tacrolimus efficiency on refractory autoimmune cytopenia patients. Dosage: 1mg bid and tacrolimus trough targets were 5-10 ng/ml throughout the study. Medication time should last at least 6 months.	Drug: Tacrolimus; On refractory autoimmune cytopenia patients, tacrolimus was tried. Dosage: 1mg bid and tacrolimus trough targets were 5-10 ng/ml throughout the study; Other Names: tacrolimus capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin level	Hemoglobin level in g/L	6 months
Platelet count	Platelet count in /L	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin level	Hemoglobin level in g/L	2 years
Platelet count	Platelet count in /L	2 years

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Bing Hang, PhD, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Li Y, Feng X. Efficacy and safety of tacrolimus in systemic lupus erythematosus patients with refractory thrombocytopenia: a retrospective study. Lupus. 2018 Jan;27(1):60-65. doi: 10.1177/0961203317711011. Epub 2017 May 31.
• Tabchi S, Hanna C, Kourie HR, Aftimos P, El Osta L, Ghosn M. Successful treatment of Evans syndrome with Tacrolimus. Invest New Drugs. 2015 Feb;33(1):254-6. doi: 10.1007/s10637-014-0155-9. Epub 2014 Sep 12. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2019
• Primary Completion (Anticipated): August 10, 2020
• Study Completion (Anticipated): November 10, 2021

Study Registration Dates

• First Submitted: April 16, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (Actual): April 17, 2019

Study Record Updates

• Last Update Posted (Actual): December 3, 2019
• Last Update Submitted That Met QC Criteria: December 1, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Tacrolimus; Prospective study; Refractory autoimmune cytopenia
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Red-Cell Aplasia, Pure; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: tacrolimus-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No